In the field of X-ray angiography utilizing an iodine compound, a technique is available which comprises administration of a water-soluble iodine-containing contrast medium for visualization of vascular flows, and detection of lesions at which the flows are obstructed. However, in the aforementioned method, the iodine-containing contrast medium is present in the vascular flows to detect changes of vascular flows inside the vessels, and the method has difficulty in distinguishing the lesions from normal tissues as compared to a method wherein an iodine-containing contrast medium is localized in cells consisting a lesion. For this reason, by the above method, only a lesion where constriction progresses 50% or more can be detected, and it is difficult to detect a lesion before the onset of attack of an ischemic disease.
Separately, attempts have also been reported in which a hydrophobic iodine-containing contrast medium or a hydrophilic contrast medium is formulated for selective accumulation in a target lesion (International Publications WO95/19186, WO95/21631, WO89/00812, British Patent No. 867650, WO96/00089, WO94/19025, WO96/40615, WO95/2295, WO98/41239, WO98/23297, WO99/02193, WO97/06132, U.S. Pat. Nos. 4,192,859, 4,567,034, 4,925,649, Pharm. Res., 6 (12), 1011 (1989); Pharm. Res., 16 (3), 420 (1999); J. Pharm. Sci., 72 (8), 898 (1983); Invest. Radiol., 18 (3), 275 (1983)). For example, Pharm. Res., 6 (12), 1011 (1989) discloses that injection of an oil-particle dispersion of cholesterol iopanoate as a hydrophobic compound allows accumulation of the iodine compound in arteriosclerotic lesions of experimental animals. Further, Pharm. Res., 16 (3), 420 (1999) discloses that administration of cholesterol iopanoate after being taken up into acetyl-LDL allows accumulation of the iodine compound in arteriosclerotic lesions of experimental animals.
Further, J. Pharm. Sci. 72 (8), 898 (1983) discloses examples of X-ray hepatography and splenography by injection of an oil-particle dispersion of cholesterol iopanoate. U.S. Pat. No. 4,567,034 describes a method of selective hepatography or splenography utilizing liposomes encapsulating an ester of diatrizoic acid. International Publications WO96/28414 and WO96/00089 disclose contrast media for imaging vascular pools or lymphatic systems. However, the methods using these formulations are not satisfactory in efficiency and selectivity for a purpose of selective contrast of vascular diseases, and no example thereof is reported in which vascular diseases are imaged by utilizing X-ray irradiation.
Further, methods have been reported in which a triglyceride compound comprising an alkylcarboxylic acid having two 3-amino-2,4,6-triiodophenyl groups and a saturated/unsaturated fatty acid is formulated as an oil particle dispersion (lipid emulsion) or a Tween 20 dispersion and used for the purpose of hepatography or imaging of blood-pool (Radiology, 216 (3) 865 (2000); Invest. Radiol., 35 (3), 158 (2000); International Publication WO98/46275; J. Pharm. Sci., 85 (9), 908 (1996); Pharm. Res., 13 (6), 875 (1996); International Publication WO95/31181; J. Med. Chem., 38 (4), 636 (1995); Invest. Radiol., 29 (SUPPL. 2), S284 (1994); International Publication WO94/19025; U.S. Pat. No. 4,873,075; Appl. Radiol. Isot., 37 (8), 907 (1986); J. Med. Chem., 29 (12), 2457 (1986)).
International Publication WO01/93918 discloses an example of radiological imaging of arteriosclerotic lesions in which a hydrophobic and hydrolysis-resistant radioactive iodine-containing contrast medium is formulated as a microemulsion or taken up into acetyl-LDL and then administered to experimental animals. Furthermore, it has been reported that the aforementioned cholesterol iopanoate is not metabolized in living bodies and accumulated in living organs, especially in liver (J. Med. Chem., 25, 1500 (1982)). The above property of the compound means that the compound remains in living bodies over a prolonged period of time, which is considered as an undesired property when a diagnostic purpose such as a contrast medium for X-ray radiography is intended.
From an aspect of compounds, U.S. Pat. No. 4,873,075 and J. Med. Chem., 29 (12), 2457 (1986) mentioned above contain descriptions of diacyl-1,3-glyceride compounds comprising an alkylcarboxylic acid containing two 3-amino-2,4,6-triiodophenyl groups and oxidized compounds thereof. However, no purpose thereof other than as synthetic intermediates is described.